The successful application of molecular and cell therapeutics to transplantable hematopoietic cells, including hematopoietic stem cells, holds the promise of life-long cures for inherited diseases of bone marrow-derived cells. The long term goal ofthe Cincinnati Center of Excellence in Molecular Hematology (CCEMH) is to understand and correct at the molecular level diseases with gene/environmental interactions affecting cells derived from hematopoietic stem cells. We believe that to attain this goal, we must understand basic biological processes that affect lympho-hematopoietic stem cell behavior in vitro and in vivo. We envision this long term goal will be accomplished by inter-disciplinary approaches using state-of-the-art molecular and cell biology methods along with timely and rational use of translational studies in the preclinical and clinical settings. Cincinnati Children's Hospital Medical Center (CCHMC), University of Cincinnati College of Medicine (UC), has developed an intellectual environment that brings together outstanding expertise in virus vector technology, stem cell biology, immune cell biology, basic research in signaling and clinical care in hematology, allergy/immunology and hematopoietic stem cell transplantation. This focus has been greatly strengthened by recruitment of over 50 faculty in these areas in the last 10 years at CCHMC and UC. The areas of basic research are linked by a newly developed and unique Translational Research Initiative, which has facilitated inter-disciplinary interactions and developed an infrastructure that is supporting state-of-the-art trials in cell and gene therapy. Thus, in this application for a new CEMH, we seek to solidify exciting and dramatic growth of research in hematology and related innate immunity/immunology at CCHMC using the shared services and administrative structure of this center grant mechanism. The CCEMH seeks to support a well developed translational research core which complements an outstanding array of basic science cores at CCHMC. These cores are functioning to support innovative research and clinical trials both locally and, in some cases nationally and internationally, in hematology and related immune-based diseases. The relevant cores include a Mouse Xenotransplant/transgenic Core, which maintains specialized mouse strains and provides mouse transplant and transgenic services, a Flow Cytometry Core that includes state-of-the-art hematology flow analysis and sorting capabilities, a Genomics &Genetics Core that support cutting edge genomic analysis of hematologic diseases and normal genetic traits of stem/progenitor cells, and a Translational Core that covers services such as ex vivo manipulation and collection of human cell products, lenti- and retrovirus production, and sophisticated preclinical assay development. Finally, this core grant seeks support for a Pilot/Feasibility program that focuses a highly successful institutional peer-reviewed pilot project initiative into hematologic and related immunologic research and an enhancement program in hosting seminars and annual retreat ofthe center.